The respiratory system plays a key function in our body, providing the oxygen necessary for the proper functioning of every cell. Due to the momentous role of this system and its close contact with all the pollutants hiding in the air, we are constantly looking for methods and substances to support the health of this system. N-acetylcysteine, also known as NAC, is a substance with well-documented effects on the lungs and the entire respiratory system. But how exactly does NAC work and what effects does it have? In this article, we take a look at the scientific evidence and research on NAC's role in the context of the respiratory system. Read to the end!

• Effects of NAC on the respiratory system
• NAC is an effective mucolytic
• Efficacy in COPD
• NAC dosage for respiratory support

Effects of NAC on the respiratory system

The pathogenesis and progression of respiratory diseases can be explained by inflammation and increased oxidative stress, which consequently leads to a decrease in endogenous antioxidants such as glutathione (GSH). For this reason, antioxidants such as NAC, which is an effective precursor to glutathione, appear to be an attractive tool in alleviating symptoms.

The use of NAC in relieving respiratory ailments is one of its main applications in medicine. NAC has a long history of use in cystic fibrosis, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. It is now readily recommended by GPs in various types of upper respiratory tract infections to relieve discomfort.

Studies have noted that NAC can raise GSH levels in neutrophils in the blood and the number of neutrophils in the respiratory tract, which promotes resistance to infection. NAC increases the secretory activity of type II follicular cells, leading to an increase in follicular surfactant, the researchers report. It also has some antimicrobial properties and the potential to reduce the risk of upper respiratory tract infections.

NAC is an effective mucolytic

NAC's mucolytic properties mean that it has the ability to reduce the rate of mucus production and viscosity. NAC produces this effect by hydrolyzing the disulfide bonds responsible for linking mucin molecules.

As a result, NAC has been approved for inhaled therapy in patients diagnosed with cystic fibrosis since the 1960s. The mucolytic effect is used both in serious lung disease and in the common cold, when excess mucus exacerbates the symptoms of infection.

Efficacy in COPD

COPD is characterized by chronic symptoms related to airway obstruction caused by inhaling toxins. It often occurs in smokers with a long history of smoking. The clinical efficacy of NAC in supporting patients with COPD has been documented in several clinical trials.

Studies with a low daily dose (600 mg max) have shown low efficacy, but there is more enthusiasm for clinical trials using higher doses. Below is a summary of the results of two studies that reported clear benefits.

1. The HIACE study - a randomized double-blind placebo-controlled trial involving 120 patients with stable chronic obstructive pulmonary disease. Fifty-eight subjects took 600 mg of oral NAC twice daily (a total of 1,200 mg per day), while 62 subjects took placebo as a control group. The study showed a significant improvement in small airway function, as well as a reduction in the frequency of disease exacerbations.
2. The PANTHEON trial - a placebo-controlled study of the efficacy and safety of high-dose NAC in COPD exacerbations. It was conducted with as many as 1006 patients with moderate to severe COPD. As part of the study, participants were orally administered 1200 mg of NAC daily. The study showed a significant reduction in the frequency of COPD exacerbations in the study group compared to the placebo group, especially in patients with moderate disease.

NAC dosage for respiratory support

For chronic diseases such as COPD that require long-term supplementation, the maximum officially recommended dose is 600 mg per day, but doses above 600 mg per day are constantly being tested in various clinical trials. In many cases of respiratory disorders, a dose of 600 mg proves to have too weak an antioxidant and anti-inflammatory effect to have a pronounced effect. Optimal efficacy is noted at doses of at least 1200 mg.

The safety profile of NAC tends to be similar, with both low doses (≤600 mg daily) and high doses (>600 mg daily). Studies with doses up to 3,000 mg daily in respiratory diseases have shown NAC to be well tolerated and safe.

Sources:

• Tenório MCDS, Graciliano NG, Moura FA, Oliveira ACM, Goulart MOF. N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel). 2021;10(6):967. Published 2021 Jun 16. doi:10.3390/antiox10060967

• Raghu G, Berk M, Campochiaro PA, et al. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol. 2021;19(8):1202-1224. doi:10.2174/1570159X19666201230144109